ArticleAutophagy2025
Histone lactylation stimulated upregulation of PSMD14 alleviates neuron PANoptosis through deubiquitinating PKM2 to activate PINK1-mediated mitophagy after traumatic brain injury.
Article in Autophagy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed.
- Lactylation: Metabolic epigenetic regulation and cell death mechanisms in myocardial ischemia‒reperfusion injury.Genes & diseases · 2027Review
- Lactate metabolism and protein lactylation in programmed cell death: From novel mechanism to therapeutic strategies in human diseases.Clinical and translational medicine · 2026Review
- Post-Translational Modifications in Traumatic Brain Injury: Decoding the Proteomic Landscape and Molecular Mechanisms of Secondary Injury.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Review
- Lactylation and regulated cell death: the substrate defines the outcome.Apoptosis : an international journal on programmed cell death · 2026Article
- Mitochondrial homeostasis imbalance-triggered PANoptosis in traumatic brain and spinal cord injury: from mechanism to therapeutic strategies.Redox biology · 2026Review
- Edaravone provides neuroprotection against chronic heat stress-induced behavioral dysfunction through adaptive proteomic remodeling.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Protein lactylation in health and diseases: molecular mechanisms, biological significance, and clinical implications.Signal transduction and targeted therapy · 2026Review
- Fenofibrate alleviates the brain edema after traumatic brain injury by enhancing endothelial OXPHOS.Redox biology · 2026Article
- Lactylation-driven therapeutic resistance in cancer: Mechanisms and therapeutic opportunities.Genes & diseases · 2026Review
- Integrative analysis of bulk and single-nucleus transcriptomes suggests proteostasis- and metabolism-related alterations in the right ventricular outflow tract of non-syndromic Tetralogy of Fallot.Functional & integrative genomics · 2026Article
- Upregulated PKM2 Protects Dopaminergic Neurons From Oxidative Damage Through Nrf2 Transactivation in an MPTP-Induced Mouse Model of Parkinson's Disease.CNS neuroscience & therapeutics · 2026Article
- Acarbose modulates microglial Pkm2 acetylation to reshape immunometabolism and preserve retinal neurons after ischemia-reperfusion.Journal of neuroinflammation · 2026Article
- The AMPK-BECN1-System Xc⁻ Pathway in Traumatic Brain Injury: Implications for Exosome-Based Therapy.Cellular and molecular neurobiology · 2026Review
- From lactate to lactylation: novel pathological mechanisms and potential therapeutic targets for high-altitude cerebral oedema.Expert reviews in molecular medicine · 2026Review
- PANoptosis as a drug discovery framework: integrating cell death architecture with clinical translation.Genes and immunity · 2026Review
- Lactylation and acetylation: parallel paths, divergent deeds, and research dilemmas.Journal of translational medicine · 2026Review
- Beyond a metabolite: lactate and lactylation in lung diseases.Respiratory research · 2026Review
- PANoptosis in diabetes: immunometabolic insights and treatments.Apoptosis : an international journal on programmed cell death · 2026Review
- Lactylation at the crossroads of metabolism and epigenetics in neuroinflammation.Frontiers in immunology · 2026Review
- Identification of Immune-Related Lactylation Genes in Rheumatoid Arthritis With Atherosclerosis: A Comprehensive Analysis Using Bulk and Single-Cell RNA Sequencing Data.Mediators of inflammation · 2026Article
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Authors and funding
12 authors.
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Abstract
Alleviating the multiple types of programmed neuronal death caused by mechanical injury has been an impetus for designing neuro-therapeutical approaches after traumatic brain injury (TBI). The aim of this study was to elucidate the potential role of PSMD14 (proteasome 26S subunit, non-ATPase 14) in neuron death and the specific mechanism through which it improves prognosis of TBI patients. Here, we identified differential expression of the PSMD14 protein between the controlled cortical impact (CCI) and sham mouse groups by LC-MS proteomic analysis and found that PSMD14 was significantly upregulated in neurons after brain injury by qPCR and western blot. PSMD14 suppressed stretch-induced neuron PANoptosis and improved motor ability and learning performance after CCI in vivo. Mechanistically, PSMD14 improved PINK1 phosphorylation levels at Thr257 and activated PINK1-mediated mitophagy by deubiquitinating PKM/PKM2 (pyruvate kinase M1/2) to maintain PKM protein stability. PSMD14-induced mitophagy promoted mitochondrial homeostasis to reduced ROS production, and ultimately inhibited the neuron PANoptosis. The upregulation of neuronal PSMD14 after TBI was due to the increase of histone lactation modification level and lactate treatment alleviated neuron PANoptosis via increasing PSMD14 expression. Our findings suggest that PSMD14 could be a potential therapeutic approach for improving the prognosis of TBI patients.
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